Protocol for chemogenetic activation of basal ganglia D1-MSNs and behavioral assessments in a primate Parkinson's disease model.

STAR Protoc

Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Research Center for Primate Neuromodulation and Neuroimaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; University of Chinese Academy of Sciences, Beijing 100049, China; Biomedical Imaging Science and System Key Laboratory, Chinese Academy of Sciences, Shenzhen 518055, China. Electronic address:

Published: December 2024

AI Article Synopsis

  • A circuit-based gene therapy has effectively reversed key symptoms of Parkinson's disease in animal models, including mice and primates.
  • This approach targets dopamine receptor D-expressing neurons through a combination of adeno-associated virus (AAV) delivery and chemogenetic techniques.
  • The research includes a step-by-step guide for AAV injection, creating PD models in primates, and evaluating the therapy's impact on motor symptoms.

Article Abstract

A circuit-based gene therapy strategy for Parkinson's disease (PD) has been shown to significantly reverse core symptoms in both murine and primate PD models. Here, we present a comprehensive workflow to specifically manipulate dopamine receptor D-expressing medium spiny neurons by retrograde adeno-associated virus (AAV) transduction and chemogenetic activation using a designer toolkit. We describe steps for AAV injections and PD primate model induction. We then detail behavioral measurements to assess the therapeutic efficacy of the therapy for motor symptoms.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656076PMC
http://dx.doi.org/10.1016/j.xpro.2024.103470DOI Listing

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